Pneumococcal disease continues to be a leading cause of sickness and death in the United States and throughout the world. The currently used polysaccharide vaccines have limited efficacy in children under 2 years of age and exhibit variable serotype-specific efficacy among vaccinated individuals. For these reasons, alternative vaccine formulations have been investigated that do not require the use of multiple capsular polysaccharides. One current approach under consideration is the use of immunogenic species-common proteins as vaccine candidates. These proteins could be used in combination with other immunogenic proteins or as protein carriers in a protein, polysaccharide, or oligosaccharide conjugate vaccine. An effective vaccine that includes a common protein could eliminate the need for formulations based on multiple capsular polysaccharides (as in the current 23-valent polysaccharide vaccine) by offering a broader range of protection against a greater number of serotypes. Additionally, a protein-based vaccine would be T-cell dependent and provide a memory response, thereby resulting in a more efficacious vaccine.
An immunogenic species-common protein has been identified from Streptococcus pneumoniae (Russell et al., 1990, “Monoclonal antibody recognizing a species-specific protein from Streptococcus pneumoniae. ”J. Clin. Microbiol., 28:2191-2195; and U.S. Pat. No. 5,422,427). A 37-kDa S. pneumoniae protein has been the focus of several studies and is now designated pneumococcal surface adhesin protein A (PsaA). (This 0.37-kDa protein was referred to as pneumococcal fimbrial protein A in U.S. Pat. No. 5,422,427; the terms are used interchangeably in the present specification.) Immunoblot analysis studies using anti-PsaA monoclonal antibody showed that PsaA is common to all 23 pneumococcal vaccine serotypes (Russell et al., 1990). Enzyme-linked-immunosorbent assay studies have indicated that patients with pneumococcal disease show an antibody increase in convalescent-phase serum to PsaA compared with acute-phase serum antibody levels (Tharpe et al., 1995, “Purification and seroreactivity of pneumococcal surface adhesin A (PsaA),” Clin. Diagn. Lab. Immunol. 3:227-229; and Tharpe et al., 1994, “The utility of a recombinant protein in an enzyme immunoassay for antibodies against Streptococcus pneumoniae,” Abstr. V-2, p 617, 1994, American Society for Microbiology, Washington, D.C.). Additionally, a limited in vivo protection study showed that antibodies to the 37-kDa protein protect mice from lethal challenge. (Talkington et al., 1996, “Protection of mice against fatal pneumococcal challenge by immunization with pneumococcal surface adhesin A (PsaA),” Microbial Pathogenesis 21:17-22). The gene encoding PsaA from S. pneumoniae strain R36A (an unencapsulated strain) has been cloned in Escherichia coli and sequenced; this strain, however, does not contain a 37-kDa protein encoding nucleic acid that is highly conserved among the various serotypes, (Sampson et al., 1994, “Cloning and nucleotide sequence analysis of PsaA, the Streptococcus pneumoniae gene encoding a 37-kilodalton protein homologous to previously reported Streptococcus sp. adhesins,” Infect. Immun. 62:319-324). This particular nucleic acid and the corresponding polypeptide, therefore, are of limited value for use as diagnostic reagents, in preventing infection, in treating infection, or in vaccine development. In U.S. patent application Ser. No. 08/715,131, filed Sep. 17, 1996, (now U.S. Pat. No. 5,854,416) which is a continuation-in-part of U.S. patent application Ser. No. 08/222,179, filed Apr. 4, 1994, which is a continuation-in-part of U.S. patent application Ser. No. 07/791,377, filed Sep. 17, 1991 (now U.S. Pat. No. 5,422,427), all of which are hereby incorporated by reference in their entirety, an isolated nucleic acid encoding the 37-kDa protein of Streptococcus pneumoniae, unique fragments of at least 10 nucleotides of this nucleic acid which can be used in methods to detect the presence of Streptococcus pneumoniae in a sample and as immunogenic vaccines have been disclosed. Furthermore, a purified polypeptide encoded by this nucleic acid, encoding the 37-kDa protein of Streptococcus pneumoniae, which can be used in immunogenic vaccines, has been disclosed. Additionally, purified antibodies which bind to the 37-kDa protein of Streptococcus pneumoniae or fragments thereof, which can be used in methods to detect the presence of Streptococcus pneumoniae, and in therapeutic and prophylactic methods, have been disclosed. Sequence conservation is a necessary requirement for a candidate species-common vaccine. The sequence conservation of the PsaA gene among pneumococcal types, and specifically among encapsulated pneumococci which cause the vast majority of cases of serious disease, remains under investigation. There exists a need to identify characteristic epitopes related to S. pneumoniae PsaA in order to provide polypeptides which can serve as a vaccine for multiple strains of Streptococcus pneumoniae. The present invention addresses this need by determining effective epitopic peptides related to S. pneumoniae PsaA, and employing those peptides in therapeutic compositions directed against Streptococcus pneumoniae infection.